Development of a pH-Responsive Antimicrobial and Potent Antioxidant Hydrogel for Accelerated Wound Healing: A Game Changer in Drug Delivery.

Stimuli-responsive hydrogels have the capability to alter their state in response to changes in physiological signals within their application environment, providing distinct benefits in drug delivery applications. Here, the acidic pH typically found in acutely infected wounds can be effectively managed by incorporating a pH-responsive Ag⁺ loaded system within the hydrogel, thereby ensuring efficient drug use and preventing potential toxicity from the sudden release of silver ions. The antimicrobial composite hydrogel HAMA/GelMA-CA/Ag⁺ provides some tissue adhesion and accelerates wound healing. GelMA-CA is synthesized by modifying gelatin methacryloyl (GelMA) with caffeic acid (CA), while hyaluronic acid methacryloyl (HAMA) is introduced to prepare a double network hydrogel. Silver nitrate is then introduced to make it pH-responsive through the formation of coordination between the polyphenolic structure of caffeic acid and the silver ions. The composite hydrogel exhibited excellent antioxidant properties and strong antimicrobial activity against both Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Furthermore, the composite hydrogel accelerated the promotion of wound healing in a rat model of S. aureus-infected wounds. In conclusion, the HAMA/GelMA-CA/Ag⁺ hydrogel is a promising bioactive material that can be used as a wound dressing to promote the healing of acutely infected wounds.